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KRAS G12V digestion by 20S proteasome

ABSTRACT: KRAS is a well known tumor associated antigen. It’s a GTPase that functions as molecular switch in regulatory pathways responsible for proliferation and survival. It’s frequently mutated in a variety of cancers. One of the possible driver mutations is G12V substitution, which impairs KRAS GTPase activity and renders the mutants persistently in the GTP-bound active form, thereby promoting tumorigenesis and tumor malignancy. Its high frequency in cancers makes KRAS an attractive target for immunotherapy. We performed in vitro digestions of synthetic polypeptide corresponding to KRAS2-35 carrying the mutation with purified 20S proteasome. Samples were measured by LC-MS/MS.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Artem Mansurkhodzhaev

LAB HEAD: Juliane Liepe

PROVIDER: PXD015580 | Pride | 2019-10-24

REPOSITORIES: Pride

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An in silico-in vitro Pipeline Identifying an HLA-A*02:01+ KRAS G12V+ Spliced Epitope Candidate for a Broad Tumor-Immune Response in Cancer Patients.

Mishto Michele M Mansurkhodzhaev Artem A Ying Ge G Bitra Aruna A Cordfunke Robert A RA Henze Sarah S Paul Debdas D Sidney John J Urlaub Henning H Neefjes Jacques J Sette Alessandro A Zajonc Dirk M DM Liepe Juliane J

Frontiers in immunology 20191115

Targeting CD8+ T cells to recurrent tumor-specific mutations can profoundly contribute to cancer treatment. Some of these mutations are potential tumor antigens although they can be displayed by non-spliced epitopes only in a few patients, because of the low affinity of the mutated non-spliced peptides for the predominant HLA class I alleles. Here, we describe a pipeline that uses the large sequence variety of proteasome-generated spliced peptides and identifies spliced epitope candid ...[more]

PMID: 31803176

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